What is MRONJ?
(MEDICATION-RELATED OSTEONECROSIS OF THE JAW)

Osteonecrosis of the jaw (dead bone) can occur when the blood supply to the upper and lower jaws is compromised and by a problem with the bone’s ability to regrow. Researchers suggest that anti-resorptive drugs lessen the body’s ability to resorb bone (osteoclastic inhibition). This is a process that naturally takes place in order to allow the formation of new bone cells (osteoblasts). When the ability to remodel and grow new bone is impaired, blood flow through the bone can be reduced or stopped. This results in bone loss, bone spurs and breaking loose of pieces of dead bone. The soft tissues around that bone and within the bone itself, which depend on that blood flow for health, also begin to die (or fail to heal). Most patients diagnosed with MRONJ have taken IV bisphosphonates (Zometa and Aredia) and Denosumab (Xgeva and Prolia) for cancer, although cases have been reported in men and post-menopausal women on Oral Bisphosphonates.

Diagnosis

Reported Signs and Symptoms of MRONJ:

• Exposed bone (more frequent in the mandible)
• Non-healing extraction site
• Undiagnosed bone pain (localized)
• Heavy jaw
• Numbness and loss of sensation
• Sudden change in health of periodontal or mucosal tissue
• Soft tissue swelling and inflammation
• Loosening of previously stable teeth
• Purulent discharge

Common Findings of Patients with MRONJ

• Presence of exposed bone in the oral cavity for 6-8 weeks
• Clinically & radiographically apparent periodontitis
• Widening of ligament around tooth, seen on x-ray as a radiolucency between teeth
• Subtle radiographic bone change, Osseous Sclerosis
• Rule out refractory osteomyelitis and osteoradionecrosis
• Rule out cysts, impactions or metastatic disease with panoramic & tomographic images
• Tissue biopsy only if metastatic disease is suspected
• Non-responsive to conservative debridement & antibiotic therapy

Prevention

Primary Risk Factors

• Underlying Bone Malignancy – Bone cancers such as multiple myeloma, breast and prostate cancer which spread to the bone
• Bisphosphonate therapy dose and duration, Denosumab (Xgeva and Prolia) dose and duration
• Intravenous more common than Oral Bisphosphonates
• Corticosteroids
• Chemotherapy, Radiotherapy
• Tooth extraction & other dental surgery (especially involving bone)
• Periodontal and dental abscesses
• Edentulous areas
• Trauma/denture sores

Secondary Risk Factors

• Vascular insufficiency due to thrombosis
• Vasoconstrictors, Anemia
• Poor oral hygiene
• Patients with osteoporosis receiving oral bisphosphonates
• Advanced age
• Women (oral bisphosphonates)
• Diabetes, Arthritis
• Alcohol abuse and Smoking

Management and Treatment

Before Starting IV Bisphosphonate Therapy (Zoledronate – Zometa, Pamidronate – Aredia) or Denosumab Therapy (Xgeva, Prolia)

Dental treatment is aimed at eliminating infections and preventing the need for invasive dental procedures in the near & intermediate future.

• Comprehensive oral examination
• Panoramic jaw X-Ray to detect dental & periodontal infection
• Individual periapical film where indicated
• If systemic conditions permit, and the patient requires bone exposing dental surgery, Bisphosphonate or Denosumab therapy should be delayed until clinical healing is complete (2-4 weeks)
• Extract non-restorable teeth with poor prognosis
• When possible, coronectomy & root canal therapy preferable to extractions
• Consider removable dentures rather than Dental Implant placement
• Periodontal surgery completed and site healed
• Treatment to eliminate infection
• Consider completing dental treatments that require bone healing
• IV Bisphosphonate or Denosumab therapy needn’t be delayed for non-invasive dental care
• Routine dental cleaning, with care to avoid soft tissue injury
• Provide routine restorative care of carious teeth
• Fluoride carriers
• Examine dentures to ensure proper fit (remove nightly)
• Educate patients on maintaining good oral hygiene:
  • A. Timely symptoms reporting
  • B. Reduce risk of dental and periodontal infection

Prophylactic antibiotics are not indicated for routine dentistry before starting bisphosphonate surgery. They may be indicated for patients with:

• Unrepaired severe congenital heart disease
• Significant heart valve problems
• History of endocarditis
• Artificial heart valve

Asymptomatic Patients on IV Bisphosphonates or Denosumab

• Continue regular dental office visits (as frequent as 3-4 months) for hard and soft tissue assessment
• Routine dental cleaning. Avoid soft tissue injury
• Non surgical management of dental infection
• Important for patient to maintain good oral hygiene
• Examine dentures to ensure proper fit (remove nightly)
• Avoid elective invasive dental procedures such as:dental implant placement
• Non restorable teeth may be treated by crown removal & endodontic treatment of remaining roots

Patients with MRONJ

• Conservative non-surgical approach directed towards eliminating or controlling pain & preventing progression of exposed bone
• Close coordination of dental & oncological care in making treatment decisions
• Oral disinfectant such as .12% Chlorhexidine
• Effective antibiotic therapy and pain control (possibly culture driven)
• Minimal surface debridement to round off sharp bony projection producing soft tissue inflammation and pain
• When patients are in pain, loose segments of bony sequestrum with exposed/necrotic bone should be removed
• Symptomatic teeth, within exposed, necrotic bone, might be considered for extraction
• Proper sterile technique
• Protective mouthguard or stent to cover exposed bone
• Removable dentures should be examined & if required adjusted to prevent soft tissue injury
• Patient instructed to clean & remove dentures at night
• When necessary, biopsy may be performed
• If possible, avoid trauma to osteonecrotic site and maintain hygiene
  • Monitor every 3 months (or less) if symptoms continue or worsen

At this time, stopping IV bisphosphonate or Denosumab therapy (in the short run) has minimal or no apparent benefit regarding MRONJ. However, if systemic conditions permit, long-term discontinuation may be beneficial in stabilizing established sites of MRONJ, reducing the risk of new site development and reducing clinical symptoms. The risk and benefits of continuing bisphosphonate therapy should be discussed with the treating oncologist in consultation with the oral and maxillofacial surgeon and patient.

General Recommendations Before and During Oral Bisphosphonate Therapy for Osteoporosis

Before Starting Oral Bisphosphonate Therapy

• Complete dental evaluation
• Inform patient of current view of low risk regarding treatment
• Can minimize risk with good oral hygiene and regular dental care
• Inform patient of treatment needed, risk of foregoing treatment and alternative treatment

Patients on Oral Bisphosphonates for Osteoporosis (Fosamax, Actonel, Boniva, Reclast)

• No specific guidelines exist for the management of patients taking oral bisphosphonates
• Treat normally. Most dental procedures will be safe
• The current opinion is that routine dental treatment generally should not be modified on basis of oral bisphosphonate therapy
• When possible, treat one tooth or quadrant at a time. Allowing 2 months healing between procedures
• Treat immediately: emergency cases, periapical pathosis, sinus tracts, purulent periodontal pockets, severe periodontitis, active abscesses
• Inform patient about dental treatment needed, associated risks and alternatives
• Document and file with patient’s chart
• The concern (as with IV bisphosphonates) is that with more women aging and taking oral bisphosphonates for longer periods of time, more cases of BRONJ may develop.

Implant placement and maintenance

• Limited data regarding MRONJ
• Avoid placing dental implants during IV Bisphosphonate or Denosumab therapy
• Patients taking oral bisphosphonates may have implants placed
• Inform patients of their treatment options, and associated risks
• Document and file in patient’s chart
• Patients should be on regular recall (monitoring) schedule

Patient may be at INCREASED risk for MRONJ when there are multiple, primary risk factors, including:

• Periodontal bone defects that are severe enough to require necessary, guided bone regeneration
• More than 3 years of Oral Bisphosphonate Therapy